The racetam family is one of the most popular groups of nootropics. Although they have similar structures, each racetam has a unique function and benefit. As a fat-soluble drug, nefiracetam can more easily pass through the blood-brain barrier when compared to water-soluble drugs like piracetam. Because of this, smaller doses appear to be effective.
Neurohackers most often compare nefiracetam to aniracetam, a common racetam nootropic utilized for its anxiolytic benefits. Some claim to experience greater improvements in mood with nefiracetam than aniracetam, although studies have not been conducted to compare their efficacy.
History of Nefiracetam
Nefiracetam is a synthetic nootropic drug derived from the original racetam, piracetam. Although it was derived from piracetam, structurally it’s more similar to aniracetam.2
Created in the 1990s, nefiracetam is one of the newer racetam nootropics. In spite of its short time on the market, it has undergone animal studies and some human studies, including clinical trials. Thus, its safety and mechanisms of action are fairly well understood.
Nootropic Benefits of Nefiracetam
Attenuates Learning and Memory Deficits
In one such study, researchers examined the effects of nefiracetam on models with cerebral ischemia. This disease is characterized by reduced blood flow to the brain that can lead to neuronal injury, neuronal death, and ischemic stroke.
The learning and memory deficits caused by the limited blood flow to the brain were improved following nefiracetam administration. The researchers believe this was thanks to restored GABA levels in the hippocampus region of the brain.4
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Memory benefits have even been found in human patients with dementia. Researchers gave dementia patients 150, 300, or 450 mg/day nefiracetam divided into three doses. Symptomatic improvements were seen in a dose-dependent manner, with 450 mg/day more effective than the lower doses.
Enhances Memory and Recall
Animal studies have found that extended supplementation with nefiracetam may help to enhance memory in healthy individuals.
In one of these studies, 15 mg/day nefiracetam was administered for 38 days in a row. Following supplementation, spatial memory and enhancements in neuronal plasticity (a marker of brain health and function) were found.5
Another study found that nefiracetam supplementation took one hour before each task increased the acquisition process, or the process of learning and forming new memories. This study supports the theory that nefiracetam enhances cognitive functions.6
Protects Against Brain Damage
After having a stroke, patients experience an increased risk of seizures, which can lead to brain damage and related memory and learning impairment. Animals studies suggest that nefiracetam may help to protect against seizures.
Researchers administered nefiracetam to an experimental stroke model. One group was given this drug prior to brain injury, while another group was given it directly following brain injury. Both of these groups experienced reductions in seizure frequency.7
In another study, researchers induced seizures in preclinical models and administered nefiracetam. While the drug did not alter the frequency of the seizures themselves, it did reduce the damage caused in the hippocampus, a region of the brain critical for memory.8
These findings demonstrate neuroprotective qualities in multiple stroke models, suggesting that nefiracetam may help to protect against stroke-induced seizures and related cognitive damage.
Promotes a Positive Mood
Strokes are known to lead to difficulties with not only memory, learning, and language, but also in mood disorders. Researchers have examined the efficacy of nefiracetam to relieve symptoms associated with mood disorders in stroke patients.
In 2008, a study was conducted on patients who had experienced a stroke within the last 3 months and were experiencing depression. 900 mg of nefiracetam was administered for 12 weeks and was found to be more effective at improving depression symptoms in most patients when compared to placebo or 600 mg nefiracetam.9
In another similar study, 900 mg of nefiracetam daily for 4 weeks was found to reduce apathy to a greater degree than 600 mg nefiracetam or placebo, while not significantly altering depression scores or cognition.10
While more studies are needed to confirm the mood benefits of nefiracetam in people who have not experienced a stroke, these findings are promising when it comes to the mood-enhancing potential of nefiracetam.
How Does It Work?
Nefiracetam works through a variety of pathways to enhance memory formation and recall, boost focus, protect neurons, and promote a calm mood.
Calcium Channel Opener
Nefiracetam increases the amount of time that the calcium channels in our brains are open, allowing an influx of calcium into our brain cells, or neurons.
The prolonged opening of calcium channels enhances long-term potentiation. This is the mechanism our brains use to create and store memories as well as boost memory and learning potential.
Enhances Excitatory Signalling
Our neurons communicate with one another using chemical molecules called neurotransmitters. There are two types of neurotransmitters: excitatory or inhibitory. Excitatory neurotransmitter signaling boosts communication between neurons, while inhibitory neurotransmitters calm this communication system.
Nefiracetam enhances the signaling of two excitatory neurotransmitters: acetylcholine (ACh) and glutamate. ACh and glutamate are both involved in memory retrieval and learning.11
Increases Acetylcholine Receptor Binding
Acetylcholine is often called the “learning neurotransmitter” thanks to its involvement in focus, memory, and learning. Nefiracetam enhances the affinity of the ACh receptor for ACh, boosting its activity and therefore its benefits.12
Regulates NMDA Signalling
The N-methyl-D-aspartate (NMDA) receptors play an important role in the central nervous system (CNS) health and the progression of certain CNS diseases.13 Nefiracetam normalizes NMDA receptor glycine signaling. It boosts signaling when glycine levels are low and attenuates it when glycine levels are high.
This allows nefiracetam to calm excess signaling of NMDA receptors using the neurotransmitter glutamate, which is known to damage brain cells. This is one way that nefiracetam may act as a neuroprotectant.
Normalizes GABA Neurotransmission
GABA is an inhibitory neurotransmitter whose action is important for relieving stress and promoting a calm mood. Nefiracetam has been found to normalize GABA activity. In other words, it enhances GABA signaling when concentrations are low and reduces signaling when concentrations are high.6
Safety and Precautions
Humans studies have demonstrated nefiracetam to be safe and non-toxic when taken at 600-900 mg/day for 4 weeks.
When side effects occur, they’re similar to those of other racetam nootropics. Some of the more common side effects include:
These side effects can be largely avoided by including a quality source of choline in your nefiracetam nootropic stack. Choline is critical for the creation of the neurotransmitter acetylcholine. Choline boosts acetylcholine synthesis. Too little choline can lead to headaches and other symptoms of choline deficiency.
If you’re looking to try this nootropic, it’s important to use it for more than one day at a time. Many of the benefits are attained following daily supplementation for at least one week. This is particularly true for the neuroprotective benefits of nefiracetam.
Nefiracetam possesses impressive abilities when it comes to protecting the health and function of the brain. It may help to reduce feelings of apathy, promote a positive mood, and help with memory formation.
Remember, if you decide to add this nootropic to your stack, you may need to supplement daily for a week or more before any significant improvements in memory will be achieved. While nefiracetam is considered safe and nontoxic in humans, you may need to include a choline supplement to avoid side effects.
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